The Histology, Biochemistry, and Molecular Imaging (HBMI) Core will provide musculoskeletal histopathology, histomorphometry, and biochemistry as well as cellular and molecular imaging and analysis services and state- of-the-art resources and training to support the collaborative clinical and basic science components of the Center for Musculoskeletal Research (CMSR), all under a single administrative structure led by Drs. Brendan F. Boyce and Jennifer H. Jonason. The HBMI Core is divided into four research and service Sub-Cores: 1) Histology, Immunohistochemistry (IHC), and In-Situ Hybridization (ISH); 2) Microscopy, Histomorphometry, and Imaging; 3) Biochemistry, Cellular, and Molecular Biology; and 4) Small Animal Surgery. Several skilled New Investigators and laboratory technicians will provide training in techniques and the use of sophisticated instrumentation within each Sub-Core. The expansion and integration of services within the HBMI Core will further increase productivity, enhance the efficiency of the Core and enable the translation between histologic and histomorphometric data and the underlying cellular and molecular mechanisms in musculoskeletal diseases. In addition, the HBMI Core will develop novel technologies and approaches to generate and analyze histologic, histomorphometric, biochemical, cellular, and molecular data in the musculoskeletal sciences, which will accelerate the pace of research for all funded projects within the CMSR. The overall Specific Aims of the Core are to: 1) provide cost-efficient and high quality histology, IHC, IF, ISH, imaging, and histomorphometry services to URRBCMBM scientists and their collaborators; 2) provide the above services at no cost to our New Investigators, who in turn will assist the Core by teaching their unique and varied skills to students and postdoctoral fellows within the CMSR; 3) provide URRBCMBM faculty and their collaborators access to state- of-the-art molecular resources, surgical equipment and suites within the HBMI Core and help New Investigators to train staff, students, and postdoctoral fellows to perform biochemical assays and small animal surgeries; and 4) innovate HBMI musculoskeletal basic and clinical research by continuing to: a) develop digital whole slide imaging WSI technology to generate novel algorithms for automated, quantitative analysis of standard and novel parameters of musculoskeletal tissue morphology and of protein and gene expression by IHC, IF or ISH in these tissues using Visiopharm's image analysis system and to validate these parameters using the OsteoMetrics, Inc. system; b) develop protocols that will enable us to quickly prepare sections of fresh samples of human tissue for isolation of high quality nucleic acids using laser capture microdissection (LCM) to support the AMP (Anolik, PI) and other grants that aim to assess gene expression levels in individual or groups of cells in diseased tissues; and c) create tissue microarrays (TMAs) of human tissues and multi- specimen blocks of murine tissues to reduce the number of slides and optimize conditions for quantitation of morphology and IHC protein expression automatically using the VS120 and Visiopharm system.